Breast Cancer
Conditions
Brief summary
This study will evaluate the safety, tolerability and efficacy of anlotinib and trastuzumab deruxtecan in human epidermal growth factor receptor 2 (HER2)-low unresectable and/or metastatic breast cancer who had received ≤1 line of prior chemotherapy.
Interventions
DRUGTrastuzumab deruxtecan
Trastuzumab deruxtecan is an antibody-drug conjugate composed of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor.
DRUGAnlotinib
Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Age 18 - 75 years; ECOG PS 0 or 1. 2. Pathologically documented breast cancer that: 1. Is unresectable or metastatic. 2. Has a history of low HER2 expression (IHC 1+& IHC 2+/ISH- or 0\<IHC\<1+). 3. Is HR-positive or HR-negative. 4. Has progressed on, and would no longer benefit from, endocrine therapy. 5. Has been treated with ≥1 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting. 3\. At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1（Previously treated lesions with radiotherapy or focal therapy and no progression cannot be included as target lesion for assessment）. 4\. Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions. 5\. Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and after the last dose for at least 6 months.
Exclusion criteria
1. Has previously been treated with anti-angiogenic targeted small molecule therapy. 2. Prior treatment with antibody drug conjugate with a topoisomerase I inhibitor exatecan derivative. 3. Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. 4. Has unresolved toxicities from previous anticancer therapy. 5. Has uncontrolled or significant cardiovascular disease. 6. Has any bleeding event, unhealed wounds, ulcerative or fractures. 7. Has arterial or venous thromboembolic events occurred within 6 months. 8. Has spinal cord compression or clinically active central nervous system metastases. 9. Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the RP2D of anlotinib in combination with trastuzumab deruxtecan | up to 1 year | The RP2D is defined as the dose level for the dose expansion phase, based on safety, tolerability, efficacy collected during the dose escalation portion of the study. |
| Objective Response Rate (ORR) | Up to approximately 3 years | ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to approximately 3 years | PFS is defined as the time from the participant's first dose of study treatment to the first date of either disease progression or death, whichever occurs first. |
| Duration of Response (DCR) | Up to approximately 3 years | DCR is defined as the percentage of cases with remission (PR+CR) and stable disease (SD) after treatment in the evaluable cases. |
| Number of Participants With Adverse Events (AEs) | Up to approximately 3 years | Assessment of the toxicity profile of regimen according to the National Cancer Institute Common Toxicity Criteria version 5.0 (NCI CTCAE v 5.0). |
| Overall Survival (OS) | Up to approximately 3 years | OS is defined as the time from the participant's first dose of study treatment to the date of death. |
| Duration of Response (DOR) | Up to approximately 3 years | DOR is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
Countries
China
Outcome results
None listed